Histopathologic Evaluation of Periapical Radiolucencies Clinico-Radiographically Diagnosed as Endodontic Lesions: A Retrospective Analysis

Statement of the Problem: Periapical cyst and granuloma are inflammatory endodontic lesions. Periapical granuloma usually heals spontaneously after endodontic treatment; however, periapical cyst mostly needs to be removed via surgical approaches. Although some clinicians believe that microscopic examination of periapical lesions is unnecessary, it is proved that some of them has non-endodontic nature that need critical consideration. Purpose: The purpose of this study was to assess the disagreement between clinico-radiographic and microscopic diagnosis of periapical cysts and granulomas in a major center of oral pathology service in Iran. Materials and Method: In this retrospective, descriptive cross-sectional study, the archives of the oral and maxillofacial pathology department of Shahid Beheshti University of Medical Sciences served as the source of the material during an 18-year-period for this retrospective, descriptive cross-sectional study. The reports of all patients whose initial clinical diagnosis was a periapical cyst/granuloma were extracted. Results: In the present study, 474 cases were diagnosed with a periapical cyst/granuloma clinico-radiographically, of which 61 cases (12.86%) received a microscopic diagnosis of a non-endodontic pathology. The most frequent lesion was odontogenic keratocyst (n= 12, 19.67%) followed by infected odontogenic cyst (n= 12, 19.67%). About 21.31% of diagnoses were non-cystic lesions and 4.9% were malignancies. The most odontogenic tumors that were diagnosed as periapical cyst/granuloma in clinico-radiography were the ameloblastoma variants (n= 4, 6.55%). Conclusion: A wide variety of microscopic diagnoses, including aggressive lesions such as ameloblastoma, as well as other malignant lesions was noted in this study. These misdiagnoses can lead to an inappropriate treatment plan. It is important to microscopically examine all lesions removed from the jaw.


Introduction
Periapical lesions are often associated with pulp necrosis leading to inflammatory reaction; however, some of them are developmental cysts and neoplasms [1][2][3][4][5][6][7].Periapical granuloma (PG) as well as common cysts of the jaws including periapical cyst (PC), dentigerous cyst (DC), residual cyst, and odontogenic keratocyst (OKC) have different clinical behaviors.They are caused by inflammatory and developmental pathogenic factors associated with the epithelium of tooth-forming apparatus.PC/PG shows a well-defined unilocular radiolucency encircles the affected tooth apex.Loss of lamina dura and a sclerotic border are also significant radiographic indicators for obtaining a diagnosis.Root resor- ption can also be observed [8].Although tooth vitality is crucial in clinical evaluation, it is important to notice that non-endodontic lesions also may lead to pulp necrosis when located adjacent to root apices.Therefore, the diagnosis cannot be made only on the vitality test of pulp and thorough evaluation of the patient including review of the patient's past medical and dental history, and accurate assessment of radiographic findings are crucial [6].It is recommended to consider cysts and neoplasms in the differential diagnosis of these lesions and to examine all surgically removed periapical lesions microscopically [6][7].The present study was conducted evaluating the discrepancy between clinic-radiographic and microscopic diagnoses in inflammatory periapical lesions.2).
In the current study, there was a predilection toward male gender and lower jaw, which was in consistent with Guimarães et al. [1] and Huang et al. [3] studies.
In the present study, DC accounted for about 16.39% of cases that diagnosed as PC/PG clinic-radiography.DC is typically characterized by a well-circumscribed unilocular radiolucency associated with the crown of an unerupted tooth with a sclerotic border and the most common differential diagnoses include OKC and ameloblastoma.However, DC may occur as a result of periapical inflammation from an overlying primary tooth and may resemble PC of a deciduous tooth; although, PCs that involve the primary tooth are so rare [18].
Three cases in the current study also showed these feat-ures in radiography (Figure 2).Huang et al. [3] and Kosanwat et al. [15] findings.Fibro-osseous lesions comprise about 4.91% of the cases, which represented from 1.27% to 15.25% in previous studies [1-3, 9, 15].It is very difficult to differentiate lesions such as focal cement-osseous dysplasia in the early stages from a PC in radiographic evaluation [19].
In addition, during the lucent phase, the periapical lamina dura is commonly lost [6].Vitality test is helpful in the differential diagnosis of these cases [19].
It is noteworthy that biopsy of cement-osseous dysplasia is not recommended in a classic presentation because of the reduced vascular supply and increased risk of post-operative infection [19].CGCG was diagnosed in two cases (3.27%) in the current study, which ranges from 1% to 11.53% in other studies [1,7,11].Dahlkemper et al. [20] mentioned that up to 20% of the CGCGs could be associated with the presence of a tooth with pulp necrosis or a previous endodontic therapy, being a significant differential diagnosis to PC/PG.
In the present study, 4.9% of histopathologic diagnoses were malignant lesions including SCC, metastatic adenocarcinoma, and LCH.The rate of malignancies was different in studies and ranged from 0% to 7% [3,[9][10][11][12]15].SCC [3], adenoid cystic carcinoma [2], and metastatic tumors [6] were mostly reported.Metastatic tumors of the jaws frequently show an ill-defined or moth-eaten radiolucency.Though, they may demonstrate non-aggressive characteristics, representing benign lesions or odontogenic infections.The past medical history may help in detecting the metastatic lesions.
However, metastatic tumors in the jaw may be the first sign of primary tumor [21].In our study, which is in line with other researches, LCH was diagnosed as a PC [3,7,9,16].LCH shows indefinite pathogenesis and a wide range of clinical manifestations and prognoses.
Oral LCH clinically may resemble severe periodontitis [22].It also can occur inside the jawbone, where they may mimic a periapical inflammatory lesion [23].Peters et al. [23] mentioned that LCH should be considered in the differential diagnosis of an apical radiolucency of vital teeth or teeth that do not respond to endodontic therapy.Dentists should be conscious of its clinical and radiographic similarities.

Conclusion
Although most of the periapical lesions has endodontic origin, this study shows a wide variety of microscopic diagnoses, including aggressive lesions such as ameloblastoma, as well as malignant lesions which was mimicking endodontic periapical lesions clinico-radiographically.This issue emphasizes the precise exploration of the patient's medical and dental histories, using vitality tests of the pulp and aspiration in clinical assessment, and detailed assessment of radiographic findings for achieving a precise diagnosis of periapical lesions.In suspected cases, a biopsy and subsequent microscopic analysis are required.

About 9 .Figure 2 :Figure 3 :
Figure 2: a: Dentigerous cyst developed around the crown of an unerupted premolar tooth diagnosed as a periapical cyst of overlying primary tooth, b: The microscopic section shows inflamed dentigerous cyst with nonkeratinized stratified squamous epithelium (Hematoxylin and eosin)

Table 1 :
Non-endodontic cysts diagnosed as PC/PG in clinic-radiography

Table 2 :
Non-cystic non-endodontic lesions diagnosed as PC/PG in clinic-radiography

Table 3 :
Frequency of non-endodontic periapical lesions (case series) reported in the literature